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Adoptive Transfer of Interleukin-21-stimulated Human CD8+ T Memory Stem Cells Efficiently Inhibits Tumor Growth

Yingshi Chen1,2,3, Fei Yu1,2,3, Yawen Jiang1,2,3

  • 1Institute of Human Virology.

Journal of Immunotherapy (Hagerstown, Md. : 1997)
|June 5, 2018
PubMed

Insights

Interleukin-21 (IL-21) effectively generates memory stem T (TSCM) cells from human CD8 T cells. These engineered TSCM cells demonstrate enhanced anti-melanoma efficacy in preclinical models.

Area of Science:

  • Immunology
  • Cell Biology
  • Cancer Therapy

Background:

  • Memory stem T (TSCM) cells possess self-renewal and multipotent properties, making them valuable for adoptive cell therapy.
  • The limited natural abundance of human TSCM cells restricts their therapeutic application.

Purpose of the Study:

  • To investigate the potential of interleukin-21 (IL-21) in inducing human CD8 TSCM cells.
  • To evaluate the therapeutic efficacy of IL-21-generated CD8 TSCM cells in a melanoma model.

Main Methods:

  • Naive CD8 T cells were stimulated with IL-21 to generate TSCM cells (defined as CD45RA+CD45RO-CD62L+CCR7+CD122+CD95+).
  • Adoptive transfer of these cells into an A375 melanoma mouse model.
  • Mechanistic studies involving the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway analysis.

Main Results:

  • IL-21 significantly enhanced the generation of CD8 TSCM cells compared to other common gamma-chain cytokines.
  • Adoptively transferred IL-21-induced TSCM cells exhibited potent antitumor responses against melanoma.
  • IL-21 modulated the JAK/STAT3 pathway, influencing the expression of key transcription factors (T-bet, SOCS1, eomesodermin, GATA3).

Conclusions:

  • IL-21 is a potent inducer of human CD8 TSCM cells.
  • IL-21-generated CD8 TSCM cells hold promise for adoptive immunotherapy against melanoma.
  • This study elucidates a novel mechanism for TSCM cell generation and highlights IL-21's therapeutic potential.

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